Once Daily Ganciclovir (ODG) as Initial Pre-Emptive Therapy (PT) Delayed until Threshold Viral Load ≥10,000 Copies/ml: A Safe and Effective Strategy for Post-Allogeneic Stem Cell Transplant (ASCT) Patients.

CMV infection is a major cause of morbidity and mortality in patients who have undergone ASCT. We previously evaluated the efficacy of ODG (5mg/kg/day) for 21 days as pre-emptive treatment for CMV viremia and found it to be effective and better tolerated than twice daily doses. We now report data evaluating ODG and PT using a quantitative CMV PCR strategy. At our institution, the detection limit of whole blood CMV PCR (WBP) is 200 copies/ml and the lower limit of quantitation 2000 copies/ml. No criteria for a standard treatment threshold currently exist for quantitative CMV PCR in plasma or whole blood. We elected to initiate treatment with ODG using a threshold WBP ≥10,000 copies/ml in clinically stable patients. Dose escalation was permitted for increasing WBP on ODG treatment. From 4/03 to 3/04, 98 patients underwent ASCT (44 related donors and 54 unrelated donors). 69/98 patients were at risk for CMV reactivation (donor/recipient CMV seropositive). Median follow-up was 318 (120–478) days post transplant. 48/69 (69.6%) patients had 1 or more episodes of CMV viremia (WBP >200 copies/ml). In 5/48 (10.4%) patients the WBP remained <10,000 copies/ml. All 5 patients cleared their viremia without treatment. 43/69 (62.3%) patients developed WBP ≥10,000 (11,324–53,000) copies/ml. 15/43 (34.9%) patients initiated treatment with BID ganciclovir (5mg/kg/BID) or foscarnet at the discretion of the treating physician. Most of these patients were acutely ill at the time of initial viremia. Two of these patients developed CMV pneumonitis which contributed to their deaths. 28/43 (65.1%) patients initiated treatment with ODG. Time to onset of viremia was a mean of 37.3 (19–62) days (>200 copies/ml) and 51.7 (27–196) days (≥10,000 copies/ml) post transplant. 10/28 patients increased ganciclovir to 5mg/kg/BID a mean of 12 (4–19) days after initiation of therapy due to increasing WBP (30,200–231,000 copies/ml). One patient developed neutropenia and was changed to foscarnet. In patients for whom WBP were available for the time points indicated, time to clearance of viremia (≤2000 copies/ml) for the 28 patients was 1/21 (5%) week 1, 8/25 (32%) week 2, 14/26 (54%) week 3, 22/27 (82%) week 4 and 26/28 (93%) week 5. Two patients did not clear their viremia at 5 weeks. One developed CMV colitis which was successfully treated. 17/28 patients remained on ODG for the 21 day treatment period. Time to clearance of viremia in this group was 1/10 (10%) week 1, 8/14 (57%) week 2, 12/15 (80%) week 3, 15/16 (94%) week 4, and 17/17 (100%) week 5. Recurrent viremia (WBP ≥10,000 copies/ml) occurred in 12/28 (43%) patients a mean of 109 (54–247) days post transplant. 2/28 (7%) patients developed CMV disease (colitis), 1 during the initial episode of viremia and 1 during a recurrence. Both were successfully treated. There were no deaths due to CMV disease in patients initiating therapy with ODG. Conclusion: Delaying treatment with ODG as initial PT until WBP ≥10,000 copies/ml is a safe and effective treatment strategy for CMV viremia post ASCT. This strategy reduces over treatment of patients and neutropenia.